1. Technical Field
The present invention relates to extractions from algae. In particular, the present invention relates to cholesterol-lowering extractions from algae and extractions that have the ability to favorably shift the HDL/LDL profile in mammals.
2. Background Art
Cholesterol is a waxy, fat-like substance made in the liver and found in certain foods, such as food from animals, like dairy products, eggs, and meat. The body needs some cholesterol in order to function properly: cell membranes, need cholesterol in order to produce hormones, such as estrogen and vitamin D, and the bile acids that help to digest fat and excrete certain waste products. However, when too much cholesterol is present, whether due to excessive dietary intake, excessive production or a decreased ability to eliminate excessive quantities, health problems such as heart disease can develop.
When too much cholesterol is present, plaque (a thick, hard deposit) can form in the body's arteries narrowing the space for blood to flow to the heart, brain and other tissues. Over time, this buildup causes atherosclerosis (hardening of the arteries), which can lead to cardiovascular diseases. When not enough oxygen-carrying blood reaches the heart, chest pain, e.g. angina, can result. If the blood supply to a portion of the heart is completely cut off by total blockage of a coronary artery, these results in the damage and death or heart cells, an event commonly called a heart attack. This is usually due to a sudden closure from a blood clot forming on top of a previous narrowing.
Lipoprotein metabolism has a key role in atherogenesis, which is the buildup of atherosclerotic plaque. Lipoprotein metabolism is a complex and interconnected group of processes that involve the receptors for lipoproteins, a family of core proteins (called apolipoproteins) around which lipids assemble to form lipoproteins, as well as the transport of lipids, particularly cholesterol and triglycerides, and their exchange between different lipoprotein classes in the blood. The intestine absorbs dietary fat and packages it into chylomicrons (large triglyceride-rich lipoproteins), which are transported to peripheral tissues through the blood. In muscle and adipose tissues, the enzyme lipoprotein lipase breaks down chylomicrons, and fatty acids enter these tissues. The chylomicron remnants are subsequently taken up by the liver. The liver loads lipids onto ApoB and secretes very-low-density lipoproteins (VLDLs), which undergo lipolysis by lipoprotein lipase to form low-density lipoproteins (LDLs). LDLs are then taken up by the liver through binding to the LDL receptor (LDLR), as well as through other pathways. By contrast, high-density lipoproteins (HDLs) are generated by the intestine and the liver through the secretion of lipid-free ApoA1. ApoA1 then recruits cholesterol from these organs through the actions of the transporter ABCA1, forming nascent HDLs, and this protects ApoA1 from being rapidly degraded in the kidneys. In the peripheral tissues, nascent HDLs promote the efflux of cholesterol from tissues, including from macrophages, through the actions of ABCA1. Mature HDLs also promote this efflux but through the actions of ABCG1. (In macrophages, the nuclear receptor LXR up-regulates the production of both ABCA1 and ABCG1, this seems out of context here) The free (unesterified) cholesterol in nascent HDLs is esterified to cholesteryl esters by the enzyme lecithin cholesterol acyltransferase (LCAT), creating mature HDLs. The cholesterol in HDLs is returned to the liver both directly, through uptake by the receptor SR-BI, and indirectly, by transfer to LDLs and VLDLs through the cholesteryl ester transfer protein (CETP). The lipid content of HDLs is altered by the enzymes hepatic lipase and endothelial lipase and by the transfer proteins CETP and phospholipid transfer protein (PLTP), affecting HDL catabolism.
LDLs can cause buildup of plaque on the walls of arteries, and their presence in large amounts indicates a risk for heart disease. HDLs in contrast, aid the body in eliminating LDLs and thus reduce heart disease. A low level of HDL also puts your body at risk for cardiovascular diseases, as the natural mechanism of eliminating LDL is reduced. Various factors can affect the amount of LDLs and HDLs that are present, such as diet, weight, exercise, age, gender, diabetes, heredity, and other medical conditions.
Statins are most commonly used to treat individuals with high cholesterol. Statins are inhibitors of the enzyme hydroxymethylglutaryl-coenzymeA reductase (HMG-CoA Reductase). Through inhibition of HMGCo Reductase, statins decrease cholesterol synthesis, and activate sterol regulatory element binding proteins (SREBPs). SREBP bind with sterol response elements (SREs). This up-regulates LDL-R gene transcription, providing an increased expression of LDL-receptors in the hepatocellular membrane and an increased cellular uptake of LDL molecules. There are several side effects reported with statin use, including myopathy, rhabdomyolysis—increased inflammation, muscle breakdown, and renal overload. Some statins, e.g. lipitor and crestor, appear to also exhibit the additional beneficial effect of inhibiting the function of CETP.
Several other treatments have been developed to combat high cholesterol, especially in food supplements. Omega-3 fatty acids are effective but lack abundant environmentally-sustainable sources. Resveratrol is a very popular treatment and is produced naturally by plants. Acai berry is also used; however, side effects are now showing up. Lingonberry and other extracts are being tested in clinical studies. Curcumin and isoflavonids are also gaining popularity. The priority of each of these supplements is to improve cardiovascular risk factors, cholesterol regulation, mental function, and weight loss.
There remains a need for a treatment for safely and effectively reducing circulating cholesterol levels and managing the HDL/LDL ratio without the incurrence of side effects. There is a further need of alternatives to current statin therapy that either have fewer deleterious side effects and/or function by a different mechanism, such as regulating cholesterol and/or lipoprotein metabolism at the genetic level.